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Study of Pembrolizumab (MK-3475) as Monotherapy in Participants With Previously-Treated Locally Advanced Unresectable or Metastatic Colorectal Cancer (MK-3475-164/KEYNOTE-164)

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ClinicalTrials.gov Identifier: NCT02460198
Recruitment Status : Active, not recruiting
First Posted : June 2, 2015
Last Update Posted : November 21, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE May 29, 2015
First Posted Date  ICMJE June 2, 2015
Last Update Posted Date November 21, 2019
Actual Study Start Date  ICMJE August 25, 2015
Actual Primary Completion Date September 9, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 11, 2018)
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST 1.1) assessed by central imaging vendor [ Time Frame: Up to approximately 2 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: May 29, 2015)
Overall Response Rate (ORR) [ Time Frame: Up to 2 years ]
Change History Complete list of historical versions of study NCT02460198 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 11, 2018)
  • Disease Control Rate (DCR) per RECIST 1.1 assessed by central imaging vendor [ Time Frame: Up to approximately 2 years ]
  • Duration of Response (DOR) per RECIST 1.1 assessed by central imaging vendor [ Time Frame: Up to approximately 2 years ]
  • Progression-Free Survival (PFS) per RECIST 1.1 assessed by central imaging vedor [ Time Frame: Up to approximately 2 years ]
  • Overall Survival (OS) [ Time Frame: Up to approximately 2 years ]
  • Number of Participants Who Experience an Adverse Event (AE) [ Time Frame: Up to approximately 27 months ]
  • Number of Participants Who Discontinue Study Treatment Due to an AE [ Time Frame: Up to approximately 2 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 29, 2015)
Disease Control Rate (DCR) [ Time Frame: Up to 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Pembrolizumab (MK-3475) as Monotherapy in Participants With Previously-Treated Locally Advanced Unresectable or Metastatic Colorectal Cancer (MK-3475-164/KEYNOTE-164)
Official Title  ICMJE A Phase II Study of Pembrolizumab (MK-3475) as Monotherapy in Subjects With Previously Treated Locally Advanced Unresectable or Metastatic (Stage IV) Mismatched Repair Deficient or Microsatellite Instability-High Colorectal Carcinoma (KEYNOTE-164)
Brief Summary

In this study, participants with previously-treated locally-advanced unresectable or metastatic mismatched repair (MMR) deficient or microsatellite instability-high (MSI-H) colorectal carcinoma (CRC) will be treated with pembrolizumab (MK-3475, KEYTRUDA®) monotherapy.

There will be two cohorts in this study: Cohort A and Cohort B. For Cohort A, participants are required to have been previously treated with standard therapies, which must include fluoropyrimidine, oxaliplatin, and irinotecan. Enrollment into Cohort A has been completed. For Cohort B, participants are required to have been previously treated with at least one line of systemic standard of care therapy: fluoropyrimidine + oxaliplatin or fluoropyrimidine + irinotecan +/ - anti-vascular endothelial growth factor (VEGF)/ epidermal growth factor regulator (EGFR) monoclonal antibody.

Detailed Description With protocol amendment 08 (13-Nov-2019), once study participants have achieved the study objective or the study has ended, participants will be discontinued from this study and may be enrolled in a pembrolizumab extension study (NCT03486873) to continue protocol-defined assessments and treatment.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Carcinoma
Intervention  ICMJE Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®
Study Arms  ICMJE
  • Experimental: Cohort A: Pembrolizumab
    Cohort A participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of every 3-week cycle (Q3W) for up to 35 cycles (up to approximately 2 years).
    Intervention: Biological: Pembrolizumab
  • Experimental: Cohort B: Pembrolizumab
    Cohort B participants receive pembrolizumab 200 mg IV on Day 1 Q3W for up to 35 cycles (up to approximately 2 years).
    Intervention: Biological: Pembrolizumab
Publications * van Vugt MJH, Stone JA, De Greef RHJMM, Snyder ES, Lipka L, Turner DC, Chain A, Lala M, Li M, Robey SH, Kondic AG, De Alwis D, Mayawala K, Jain L, Freshwater T. Immunogenicity of pembrolizumab in patients with advanced tumors. J Immunother Cancer. 2019 Aug 8;7(1):212. doi: 10.1186/s40425-019-0663-4.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: January 11, 2018)
124
Original Estimated Enrollment  ICMJE
 (submitted: May 29, 2015)
60
Estimated Study Completion Date  ICMJE August 10, 2020
Actual Primary Completion Date September 9, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

  • Histologically-proven locally advanced unresectable or metastatic high colorectal carcinoma
  • Locally confirmed MMR deficient or MSI-H status
  • Has been previously treated with standard therapies, which must include, for Cohort A, fluoropyrimidine, oxaliplatin, and irinotecan, and for Cohort B, at least one line of systemic standard of care therapy: fluoropyrimidine + oxaliplatin or fluoropyrimidine + irinotecan +/- anti-VEGF/EGFR monoclonal antibody (mAb).
  • Eastern Cooperative Oncology Group performance status of 0 or 1
  • Life expectancy of greater than 3 months
  • Provides an archival or newly obtained (≤60 days prior to first dose of study treatment) tumor tissue sample (Cohort B)
  • At least one measureable lesion
  • Female participants of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study treatment
  • Male participants should agree to use an adequate method of contraception starting with the first dose of study treatment through 120 days after the last dose of study treatment
  • Adequate organ function

Exclusion criteria:

  • Currently participating in another study and receiving trial treatment, participated in a study of an investigational agent and received trial treatment within 4 weeks of the first dose of treatment in this study, or used an investigational device within 4 weeks of the first dose of treatment in this study
  • Active autoimmune disease that has required systemic treatment in past 2 years
  • Diagnosis of immunodeficiency or is receiving systemic steroid therapy in dosing exceeding 10 mg daily of prednisone equivalent or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
  • Known active central nervous system metastases and/or carcinomatous meningitis
  • Prior mAb, chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or not recovered (i.e., ≤ Grade 1 or at baseline) from AEs due to a previously administered agent
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, OR other immune check point agonist/inhibitor
  • Has a known additional malignancy that is progressing or requires active treatment within the past 3 years. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  • Received a live vaccine within 30 days of planned start of study treatment
  • Known history of human immunodeficiency virus (HIV)
  • Known active Hepatitis B or C
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
  • Active infection requiring systemic therapy
  • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
  • Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment
  • Has a history of severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Australia,   Belgium,   Canada,   France,   Germany,   Israel,   Japan,   Korea, Republic of,   Spain,   United States
 
Administrative Information
NCT Number  ICMJE NCT02460198
Other Study ID Numbers  ICMJE 3475-164
2015-001852-32 ( EudraCT Number )
153046 ( Registry Identifier: JAPIC-CTI )
MK-3475-164 ( Other Identifier: Merck Protocol Number )
KEYNOTE-164 ( Other Identifier: Merck )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP